CELLULAR UPTAKE AS A DETERMINANT OF CYTOTOXICITY OF QUATERNIZED ELLIPTICINES TO HUMAN BRAIN-TUMOR CELLS

The quaternized ellipticine derivative, 9-methoxy-N-2-methylellipticinium acetate (MMEA), is representative of a group of ellipticinium compounds found preferentially cytotoxic to human brain tumor cell lines comprising a subpanel of the U.S. National Cancer Institute (NCI)'s in vitro ''disease-oriented'' anticancer drug discovery screen. The present studies indicate that the accumulation and cytotoxicity of MMEA in these susceptible cells are mediated in part by a cellular transport process having substrate and inhibitor specificities similar to those found in glial-derived cells which presumably comprise part of the structural (non-neuronal) elements of normal brain.